The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models
Open accessAbstract
Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP), across a large age range (9-26 months), with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.
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Cites
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
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[ 11 C]PIB in a nondemented population: Potential antecedent marker of Alzheimer disease
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Self-citationBard, F., Barbour, R., Cannon, C., Carretto, R., Fox, M., Games, D., Guido, T., Hoenow, K., Hu, K., Johnson-Wood, K., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0436286100 · Cited by 411
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Aβ peptide immunization restores blood‐brain barrier integrity in Alzheimer disease
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“Despite promising advances in immunotherapeutics [17,30,31,32,33] and PET imaging [34,35,36], Alzheimer’s disease remains intractable to current therapeutic and diagnostic strategies.”
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Cited by
Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound
Lipsman, N., Meng, Y., Bethune, A. J., Huang, Y., Lam, B., Masellis, M., Herrmann, N., Heyn, C., Aubert, I., Boutet, A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-04529-6 · Cited by 950
Self-citationThe blood-brain barrier: Physiology and strategies for drug delivery
Pandit, R., Chen, L., & Götz, J. (2020) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2019.11.009 · Cited by 651
Nanotechnological advances for the delivery of cns therapeutics.
Wong, H. L., Wu, X. Y., & Bendayan, R. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.10.007 · Cited by 488
Aryal, M., Arvanitis, C. D., Alexander, P. M., & McDannold, N. (2014) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2014.01.008 · Cited by 443
Self-citationEvolving Drug Delivery Strategies to Overcome the Blood Brain Barrier
S. Hersh, D., S. Wadajkar, A., B. Roberts, N., G. Perez, J., P. Connolly, N., Frenkel, V., A. Winkles, J., F. Woodworth, G., & J. Kim, A. (2016) · Current Pharmaceutical Design · doi:10.2174/1381612822666151221150733 · Cited by 387
Metadata
- Authors
- Raymond, S. B., Treat, L. H., Dewey, J. D., McDannold, N. J., Hynynen, K., & Bacskai, B. J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-05-14
- Volume
- 3
- Issue
- 5
- Pages
- e2175
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2114072420
- Cited by
- 227
- References
- 8
- FWCI
- 9.17
- Type
- journal article
- Language
- en
- Open access
- gold
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- Raymond, S. B., Treat, L. H., Dewey, J. D., McDannold, N. J., Hynynen, K., & Bacskai, B. J. (2008). Ultrasound Enhanced Delivery of Molecular Imaging and Therapeutic Agents in Alzheimer's Disease Mouse Models. PLoS ONE. https://doi.org/10.1371/journal.pone.0002175
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